Evaluating the role of pathogenic dementia variants in posterior cortical atrophy

Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to “posterior Alzheimer's disease (AD)” pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes in PCA, we screened 124 European-American subjects with clinical PCA (n = 67) or posterior AD neuropathology (n = 57) for variants in genes implicated in AD, frontotemporal dementia, and prion disease using NeuroX, a customized exome array. Frequencies in PCA of the variants annotated as pathogenic or potentially pathogenic were compared against ∼4300 European-American population controls from the NHLBI Exome Sequencing Project. We identified 2 rare variants not previously reported in PCA, TREM2 Arg47His, and PSEN2 Ser130Leu. No other pathogenic or potentially pathogenic variants were detected in the screened dementia genes. In this first systematic variant screen of a PCA cohort, we report 2 rare mutations in TREM2 and PSEN2, validate our previously reported APOE ε4 association, and demonstrate the utility of NeuroX

The second step in the construction of a stigma scale of scale

Rationale: The issue of stigmatization is one of the most common psychosocial problems faced by people with epilepsy. Purpose: A second step towards the development of a scale to measure epilepsy stigma. Method: We applied a closed questionnaire to 12 patients and 32 relatives from the Epilepsy Outpatient Clinic at the University Hospital of Campinas. Results: The results are grouped in three main domains: medical, social and personal areas. Medical: the subjects did not know exactly what epilepsy is or how it is caused; nonetheless they know how to treat it. Social: the most important areas that people with epilepsy are discriminated are at work and social relationships. Patients also complained about their lack of freedom and limits on recreation activities. Personal Area: subjects apparently have the same feelings and thoughts about epilepsy and seizures. Conclusion: This study analyzed the most common aspects presented in the questionnaire to assess epilepsy stigma for the Brazilian culture which are the base to the elaboration of a stigma scale of epilepsy.632B39539

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Antiviral activity of Fridericia formosa (Bureau) L. G. Lohmann (Bignoniaceae) extracts and constituents.

A phytochemical study of Fridericia formosa (Bignoniaceae) ethanol extracts of leaves, stems, and fruits was guided by in vitro assays against vaccinia virus Western Reserve (VACV-WR), human herpes virus 1 (HSV-1), murine encephalomyocarditis virus (EMCV), and dengue virus type 2 (DENV-2) by the MTT method. All the ethanol extracts were active against DENV-2, HSV-1, and VACV-WRwith best results for the fruits extract against DENV-2 (SI > 38.2). For VACV-WRand HSV-1, EC50 values > 200 ?g mL?1 were determined, while no inhibition of the cytopathic effect was observed with EMCV. Five compounds were isolated and identified as the C-glucosylxanthones mangiferin (1), 2?-O-trans-caffeoylmangiferin (2), 2?-O-trans-coumaroylmangiferin (3), 2?- O-trans-cinnamoylmangiferin (5), and the flavonoid chrysin (4). The most active compound was 2?-O-trans-coumaroylmangiferin (3) with SI > 121.9 against DENV-2 and 108.7 for HSV-1. These results indicate that mangiferin cinnamoyl esters might be potential antiviral drugs

Perinatal outcomes among births to women with infection during pregnancy

Objective This study is part of the Global Maternal Sepsis Study (GLOSS). It aimed to estimate neonatal near-miss (NNM) and perinatal death frequency and maternal risk factors among births to women with infection during pregnancy in low-income and middle-income countries (LMIC). Design We conducted a 1-week inception hospital-based cohort study. Setting The study was carried out in 408 hospitals in 43 LMIC of all the WHO regions in 2017. Patients We included women with suspected or confirmed infection during pregnancy with at least 28 weeks of gestational age up to day-7 after birth. All babies born to those women were followed from birth until the seventh day after childbirth. Perinatal outcomes were considered at the end of the follow-up. Main outcome measures Perinatal outcomes were (i) babies alive without severe complication, (ii) NNM and (iii) perinatal death (stillbirth and early neonatal death). Results 1219 births were analysed. Among them, 25.9% (n=316) and 10.1% (n=123) were NNM and perinatal deaths, respectively. After adjustment, maternal pre-existing medical condition (adjusted odds ratios (aOR)=1.5; 95% CI 1.1 to 2.0) and maternal infection suspected or diagnosed during labour (aOR=1.9; 95% CI 1.2 to 3.2) were the independent risk factors of NNM. Maternal pre-existing medical condition (aOR=1.7; 95% CI 1.0 to 2.8), infection-related severe maternal outcome (aOR=3.8; 95% CI 2.0 to 7.1), mother's infection suspected or diagnosed within 24 hours after childbirth (aOR=2.2; 95% CI 1.0 to 4.7) and vaginal birth (aOR=1.8; 95% CI 1.1 to 2.9) were independently associated with increased odds of perinatal death. Conclusions Overall, one-third of births were adverse perinatal outcomes. Pre-existing maternal medical conditions and severe infection-related maternal outcomes were the main risk factors of adverse perinatal outcomes

Pharmaceutical services for endemic situations in the Brazilian Amazon: organization of services and prescribing practices for Plasmodium vivax and Plasmodium falciparum non-complicated malaria in high-risk municipalities

<p>Abstract</p> <p>Background</p> <p>In spite of the fact that pharmaceutical services are an essential component of all malaria programmes, quality of these services has been little explored in the literature. This study presents the first results of the application of an evaluation model of pharmaceutical services in high-risk municipalities of the Amazon region, focusing on indicators regarding organization of services and prescribing according to national guidelines.</p> <p>Methods</p> <p>A theoretical framework of pharmaceutical services for non-complicated malaria was built based on the Rapid Evaluation Method (WHO). The framework included organization of services and prescribing, among other activities. The study was carried out in 15 primary health facilities in six high-risk municipalities of the Brazilian Amazon. Malaria individuals ≥ 15 years old were approached and data was collected using specific instruments. Data was checked by independent reviewers and fed to a data bank through double-entry. Descriptive variables were analyzed.</p> <p>Results</p> <p>A copy of the official treatment guideline was found in 80% of the facilities; 67% presented an environment for receiving and prescribing patients. Re-supply of stocks followed a different timeline; no facilities adhered to forecasting methods for stock management. No shortages or expired anti-malarials were observed, but overstock was a common finding. On 86.7% of facilities, the average of good storage practices was 48%. Time between diagnosis and treatment was zero days. Of 601 patients interviewed, 453 were diagnosed for <it>Plasmodium vivax</it>; of these, 99.3% received indications for the first-line scheme. Different therapeutic schemes were given to <it>Plasmodium falciparum </it>patients. Twenty-eight (4.6%) out of 601 were prescribed regimens not listed in the national guideline. Only 5.7% individuals received a prescription or a written instruction of any kind.</p> <p>Conclusions</p> <p>The results show that while diagnostic procedure is well established and functioning in the Brazilian malaria programme, prescribing is still an activity that is actually not performed. The absence of physicians and poor integration between malaria services and primary health services make for the lack of a prescription or written instruction for malaria patients throughout the Brazilian Amazon. This fact may lead to a great number of problems in rational use and in adherence to medication.</p

Synthesis by click reactions and antiplasmodial activity of Lupeol 1,2,3-Triazole derivatives.

Lupeol, a triterpene frequently found in Asteraceae plant species, showed moderate to low activity in different strains of Plasmodium falciparum, the most virulent malaria etiological agents. In this work, lupeol was isolated from Parahancornia fasciculata, a plant that is used to treat malaria in the Amazonia region. In the search of more activity lupeol derivatives, five new 1,2,3-triazole hybrid molecules were synthetized by copper-catalyzed azide-alkyne cycloaddition. The antiplasmodial activity of the semi-synthetic compounds were evaluated by the lactate dehydrogenase assay; the lupeol propargyl ether was the only one to disclosing increased activity (half maximal inhibitory concentration-IC50-62.0 ? 1.92 ?mol L-1) in relation to lupeol (IC50 117.00 ?mol L-1). Therefore, this work revealed a new class of interesting lupeol derivatives that can be obtained by linking electron donors to the hydroxy group at C-3